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Mowat-Wilson syndrome

Reviewed December 2007

What is Mowat-Wilson syndrome?

Mowat-Wilson syndrome is a genetic condition that affects many parts of the body. Major signs of this disorder frequently include distinctive facial features, intellectual disability, delayed development, an intestinal disorder called Hirschsprung disease, and other birth defects.

Children with Mowat-Wilson syndrome have a square-shaped face with deep-set, widely spaced eyes. They also have a broad nasal bridge with a rounded nasal tip; a prominent and pointed chin; large, flaring eyebrows; and uplifted earlobes with a dimple in the middle. These facial features become more distinctive with age, and adults with Mowat-Wilson syndrome have an elongated face with heavy eyebrows and a pronounced chin and jaw. Affected people tend to have a smiling, open-mouthed expression, and they typically have friendly and happy personalities.

Mowat-Wilson syndrome is often associated with an unusually small head (microcephaly), structural brain abnormalities, and intellectual disability ranging from moderate to severe. Speech is absent or severely impaired, and affected people may learn to speak only a few words. Many people with this condition can understand others' speech, however, and some use sign language to communicate. If speech develops, it is delayed until mid-childhood or later. Children with Mowat-Wilson syndrome also have delayed development of motor skills such as sitting, standing, and walking.

More than half of people with Mowat-Wilson syndrome are born with an intestinal disorder called Hirschsprung disease that causes severe constipation, intestinal blockage, and enlargement of the colon. Chronic constipation also occurs frequently in people with Mowat-Wilson syndrome who have not been diagnosed with Hirschsprung disease.

Other features of Mowat-Wilson syndrome include short stature, seizures, heart defects, and abnormalities of the urinary tract and genitalia. Less commonly, this condition can also affect the eyes, teeth, hands, and skin coloring (pigmentation). Although many different medical issues have been associated with Mowat-Wilson syndrome, not every individual with this condition has all of these features.

How common is Mowat-Wilson syndrome?

The prevalence of Mowat-Wilson syndrome is unknown. At least 170 people with this condition have been reported.

What genes are related to Mowat-Wilson syndrome?

Mutations in the ZEB2 gene cause Mowat-Wilson syndrome.

The ZEB2 gene provides instructions for making a protein that plays a critical role in the formation of many organs and tissues before birth. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Researchers believe that the ZEB2 protein is involved in the development of tissues that give rise to the nervous system, digestive tract, facial features, heart, and other organs.

Mowat-Wilson syndrome almost always results from a loss of one working copy of the ZEB2 gene in each cell. In some cases, the entire gene is deleted. In other cases, mutations within the gene lead to the production of an abnormally short, nonfunctional version of the ZEB2 protein. A shortage of this protein disrupts the normal development of many organs and tissues, which causes the varied signs and symptoms of Mowat-Wilson syndrome.

Related Gene(s)

Changes in this gene are associated with Mowat-Wilson syndrome.

  • ZEB2

How do people inherit Mowat-Wilson syndrome?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of Mowat-Wilson syndrome?

These resources address the diagnosis or management of Mowat-Wilson syndrome and may include treatment providers.

  • Gene Review: Mowat-Wilson Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=mws)
  • Genetic Testing Registry: Mowat-Wilson syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1856113)
  • MedlinePlus Encyclopedia: Hirschsprung's Disease (http://www.nlm.nih.gov/medlineplus/ency/article/001140.htm)

You might also find information on the diagnosis or management of Mowat-Wilson syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/mowat-wilson-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/mowat-wilson-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Mowat-Wilson syndrome?

You may find the following resources about Mowat-Wilson syndrome helpful. These materials are written for the general public.

  • MedlinePlus - Health information

    • Encyclopedia: Hirschsprung's Disease (http://www.nlm.nih.gov/medlineplus/ency/article/001140.htm)
    • Health Topic: Colonic Diseases (http://www.nlm.nih.gov/medlineplus/colonicdiseases.html)
    • Health Topic: Congenital Heart Defects (http://www.nlm.nih.gov/medlineplus/congenitalheartdefects.html)
    • Health Topic: Developmental Disabilities (http://www.nlm.nih.gov/medlineplus/developmentaldisabilities.html)
  • Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/gard/9673/resources/resources/1)

  • Additional NIH Resources - National Institutes of Health

    • Eunice Kennedy Shriver National Institute of Child Health and Human Development: Intellectual and Developmental Disabilities (http://www.nichd.nih.gov/health/topics/idds/Pages/default.aspx)
    • National Institute of Diabetes and Digestive and Kidney Diseases: What I Need to Know About Hirschsprung's Disease (http://digestive.niddk.nih.gov/ddiseases/pubs/hirschsprungs_ez/)

  • Educational resources - Information pages

    • Centre for Genetics Education (Australia) (http://www.mowatwilson.org/Biography%20Files/MOWAT-WILSON%20SYNDROME%2012-05.pdf)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=2152)

  • Patient support - For patients and families

    • Congenital Heart Information Network (http://tchin.org/)
    • International Foundation for Functional Gastrointestinal Disorders (http://www.aboutkidsgi.org/)
    • National Organization for Rare Disorders (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1148/viewAbstract)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=mws)

  • Genetic Testing Registry - Repository of genetic test information

    • Genetic Testing Registry: Mowat-Wilson syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1856113)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((mowat-wilson%20syndrome%5BTIAB%5D)%20OR%20(hirschsprung%20disease-mental%20retardation%20syndrome%5BTIAB%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/235730)

What other names do people use for Mowat-Wilson syndrome?

  • Hirschsprung Disease-Mental Retardation Syndrome
  • Microcephaly, Mental Retardation, and Distinct Facial Features, with or without Hirschsprung disease
  • MWS

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Mowat-Wilson syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Mowat-Wilson syndrome?

agenesis ; autosomal ; autosomal dominant ; cell ; chronic ; colon ; constipation ; corpus callosum ; digestive ; DNA ; gene ; genitalia ; hypertelorism ; mental retardation ; microcephaly ; motor ; nervous system ; neural crest ; pigmentation ; prevalence ; protein ; short stature ; sign ; sign language ; stature ; syndrome ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Adam MP, Schelley S, Gallagher R, Brady AN, Barr K, Blumberg B, Shieh JT, Graham J, Slavotinek A, Martin M, Keppler-Noreuil K, Storm AL, Hudgins L. Clinical features and management issues in Mowat-Wilson syndrome. Am J Med Genet A. 2006 Dec 15;140(24):2730-41. (http://www.ncbi.nlm.nih.gov/pubmed/17103451?dopt=Abstract)
  • Garavelli L, Donadio A, Zanacca C, Banchini G, Della Giustina E, Bertani G, Albertini G, Del Rossi C, Zweier C, Rauch A, Zollino M, Neri G. Hirschsprung disease, mental retardation, characteristic facial features, and mutation in the gene ZFHX1B (SIP1): confirmation of the Mowat-Wilson syndrome. Am J Med Genet A. 2003 Feb 1;116A(4):385-8. (http://www.ncbi.nlm.nih.gov/pubmed/12522797?dopt=Abstract)
  • Garavelli L, Mainardi PC. Mowat-Wilson syndrome. Orphanet J Rare Dis. 2007 Oct 24;2:42. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17958891?dopt=Abstract)
  • Gene Review: Mowat-Wilson Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=mws)
  • Ishihara N, Yamada K, Yamada Y, Miura K, Kato J, Kuwabara N, Hara Y, Kobayashi Y, Hoshino K, Nomura Y, Mimaki M, Ohya K, Matsushima M, Nitta H, Tanaka K, Segawa M, Ohki T, Ezoe T, Kumagai T, Onuma A, Kuroda T, Yoneda M, Yamanaka T, Saeki M, Segawa M, Saji T, Nagaya M, Wakamatsu N. Clinical and molecular analysis of Mowat-Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22-q24.1. J Med Genet. 2004 May;41(5):387-93. (http://www.ncbi.nlm.nih.gov/pubmed/15121779?dopt=Abstract)
  • Mowat DR, Wilson MJ, Goossens M. Mowat-Wilson syndrome. J Med Genet. 2003 May;40(5):305-10. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12746390?dopt=Abstract)
  • Wilson M, Mowat D, Dastot-Le Moal F, Cacheux V, Kääriäinen H, Cass D, Donnai D, Clayton-Smith J, Townshend S, Curry C, Gattas M, Braddock S, Kerr B, Aftimos S, Zehnwirth H, Barrey C, Goossens M. Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B. Am J Med Genet A. 2003 Jun 15;119A(3):257-65. (http://www.ncbi.nlm.nih.gov/pubmed/12784289?dopt=Abstract)
  • Zweier C, Albrecht B, Mitulla B, Behrens R, Beese M, Gillessen-Kaesbach G, Rott HD, Rauch A. "Mowat-Wilson" syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene. Am J Med Genet. 2002 Mar 15;108(3):177-81. (http://www.ncbi.nlm.nih.gov/pubmed/11891681?dopt=Abstract)
  • Zweier C, Temple IK, Beemer F, Zackai E, Lerman-Sagie T, Weschke B, Anderson CE, Rauch A. Characterisation of deletions of the ZFHX1B region and genotype-phenotype analysis in Mowat-Wilson syndrome. J Med Genet. 2003 Aug;40(8):601-5. (http://www.ncbi.nlm.nih.gov/pubmed/12920073?dopt=Abstract)
  • Zweier C, Thiel CT, Dufke A, Crow YJ, Meinecke P, Suri M, Ala-Mello S, Beemer F, Bernasconi S, Bianchi P, Bier A, Devriendt K, Dimitrov B, Firth H, Gallagher RC, Garavelli L, Gillessen-Kaesbach G, Hudgins L, Kääriäinen H, Karstens S, Krantz I, Mannhardt A, Medne L, Mücke J, Kibaek M, Krogh LN, Peippo M, Rittinger O, Schulz S, Schelley SL, Temple IK, Dennis NR, Van der Knaap MS, Wheeler P, Yerushalmi B, Zenker M, Seidel H, Lachmeijer A, Prescott T, Kraus C, Lowry RB, Rauch A. Clinical and mutational spectrum of Mowat-Wilson syndrome. Eur J Med Genet. 2005 Apr-Jun;48(2):97-111. Epub 2005 Feb 25. (http://www.ncbi.nlm.nih.gov/pubmed/16053902?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2007
Published: May 13, 2013